Rimegepant (Monograph)

Brand name: Nurtec
Drug class: Calcitonin Gene-related Peptide (CGRP) Antagonists
- CGRP Receptor Antagonists
- Gepants
- Small-molecule Calcitonin Gene-related Peptide Receptor Antagonists
Chemical name: [(5S,6S,9R)-5-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl] 4-(2-oxo-3H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate
Molecular formula: 2C₂₈H₂₈F₂N₆O₃•H₂SO₄•3H₂O
CAS number: 1374024-48-2

Medically reviewed by Drugs.com on Mar 15, 2024. Written by ASHP.

Introduction

Antimigraine agent; small molecule calcitonin gene-related peptide receptor (CGRP) receptor antagonist (gepant).

Uses for Rimegepant

Acute Treatment of Migraine

Acute treatment of migraine with or without aura in adults.

In clinical studies, rimegepant was more effective than placebo in relieving migraine pain and the patient's most bothersome symptoms (e.g., photophobia, phonophobia, nausea) at 2 hours post-dose.

The American Headache Society (AHS) guidelines include the oral CGRP antagonists (gepants) as one of several drugs with established efficacy in the acute treatment of migraine. Unlike 5-HT₁ receptor agonists (triptans) and ergot alkaloids, CGRP antagonists do not cause constriction of blood vessels, and therefore may have a role in patients with cardiovascular contraindications to triptans. Because of the relatively high cost of CGRP antagonists compared with oral triptans in the acute treatment of migraine, AHS recommends that oral CGRP antagonists be considered for use only in patients who have contraindications to the use of triptans and/or who have an inadequate response or intolerance to at least 2 oral triptans.

Preventive Treatment of Migraine

Preventive treatment of episodic migraine in adults.

Current guidelines from the American Headache Society (AHS) discuss the evidence for rimegepant in the preventive treatment of migraines. AHA states that use of gepants should be based on regimens used in clinical trials and individualized according to the needs of each patient. Repeated treatment with these drugs does not appear to be associated with medication overuse headache or liver toxicity.

Related/similar drugs

Aimovig, Botox, acetaminophen, ibuprofen, amitriptyline, naproxen, diclofenac

Rimegepant Dosage and Administration

Administration

Oral Administration

Administer orally without regard to food.

Commercially available as orally disintegrating tablets. Instruct patients to use dry hands to peel back the foil covering of one blister and gently remove the tablet. Do not push the tablet through the foil. The tablet should immediately be placed on or under the tongue, where it disintegrates in saliva and can be swallowed without additional liquid. Once the blister is opened, the tablet should be taken immediately; do not store tablet outside the blister packaging for future use.

Dosage

Dosage of rimegepant sulfate is expressed in terms of rimegepant.

Adults

Acute Treatment of Migraine

Oral

75 mg as needed. Maximum dose in a 24-hour period is 75 mg.

Safety of using more than 18 doses in a 30-day period not established.

Preventive Treatment of Migraine

Oral

75 mg once every other day.

Dosage Modification for Drug Interactions

Oral

Avoid taking another dose of rimegepant within 48 hours if used concomitantly with a moderate CYP3A4 inhibitor.

Avoid concomitant use of potent CYP3A4 inhibitors, moderate or potent CYP3A inducers, P-glycoprotein (P-gp) inhibitors, and/or breast cancer resistance protein (BCRP) inhibitors.

Prescribing Limits

Adults

Acute Treatment of Migraine

Oral

Maximum dose in a 24-hour period is 75 mg.

Safety of using more than 18 doses in a 30-day period not established.

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment: Dosage adjustment not necessary.

Severe hepatic impairment: Avoid use.

Renal Impairment

Mild, moderate, or severe renal impairment: Dosage adjustment not necessary.

End-stage renal disease or dialysis: Avoid use.

Cautions for Rimegepant

Contraindications

• History of hypersensitivity reaction to rimegepant or any ingredient in the formulation.

Warnings/Precautions

Hypersensitivity

Hypersensitivity reactions, including dyspnea and rash, reported. Delayed serious hypersensitivity reactions (e.g., days after administration) also have occurred.

If a hypersensitivity reaction occurs, discontinue drug and initiate appropriate therapy.

Specific Populations

Pregnancy

No adequate data on the developmental risk associated with use of rimegepant in pregnant women. Adverse developmental effects observed in animal studies.

Possible increased risk of preeclampsia and gestational hypertension during pregnancy in women with migraine.

Lactation

Not known whether distributed into milk. Effects on the breast-fed infant or on milk production also unknown. Consider developmental and health benefits of breast-feeding, mother's clinical need for the drug, and potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; no clinically important pharmacokinetic differences observed.

Hepatic Impairment

Mild or moderate (Child-Pugh class A or B) hepatic impairment: No dosage adjustment necessary.

Severe (Child-Pugh class C) hepatic impairment: Avoid use.

Renal Impairment

Mild, moderate, or severe renal impairment (Cl_cr 15–89 mL/minute): No dosage adjustment necessary.

End-stage renal disease (Cl_cr <15 mL/minute) or requiring dialysis: Not studied; avoid use.

Pharmacogenomic Considerations

Genetic polymorphism of CYP2C9 (e.g., normal metabolizers [*1/*1 genotype], intermediate metabolizers [*1/*2, *2/*2, *1/*3 genotypes]) is not expected to have clinically important effects on rimegepant exposure.

No adequate data in poor CYP2C9 metabolizers (*2/*3 genotype).

Common Adverse Effects

Acute treatment of migraine (≥1%): Nausea.

Preventive treatment of migraine (≥2%): Nausea, abdominal pain/dyspepsia.

Drug Interactions

Metabolized principally by CYP3A4 and, to a lesser extent, CYP2C9. Weak inhibitor of CYP3A4 with time-dependent inhibition in vitro. Does not inhibit CYP1A2, 2B6, 2C9, 2C19, 2D6, or UGT1A1 or induce CYP1A2, 2B6, or 3A4 at clinically relevant concentrations.

Substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Clinically important drug interactions not expected with other drug transporters at clinically relevant concentrations.

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP3A4 Inhibitors: Possible substantially increased rimegepant exposure. Avoid concomitant use.

Moderate CYP3A4 Inhibitors: Possible increased rimegepant exposure; less than twofold increase expected. In patients receiving a moderate CYP3A4 inhibitor, do not administer multiple doses of rimegepant within 48 hours of each other.

CYP2C9 Inhibitors: Clinically important effects on rimegepant exposure not expected.

Moderate or potent CYP3A4 Inducers: Possible substantially decreased rimegepant exposure and efficacy. Avoid concomitant use.

Weak CYP3A4 Inducers: Clinically important effects on rimegepant exposure not expected.

Drugs Affecting P-gp or BCRP

Possible substantially increased rimegepant exposure. Avoid concomitant use.

Specific Drugs

Rimegepant Pharmacokinetics

Absorption

Bioavailability

Absolute oral bioavailability: Approximately 64%.

Food

Administration with high-fat meal delays time to peak plasma concentration by 1 hour and decreases peak plasma concentration and AUC by 42–53 and 32–38%, respectively; clinical importance not known. Rimegepant was administered without regard to food in clinical studies.

Special Populations

Mild or moderate hepatic impairment (Child-Pugh class A or B): No clinically important effect on systemic exposure.

Severe hepatic impairment (Child-Pugh class C): Approximately twofold higher systemic exposure.

Moderate renal impairment (Cl_cr 30–59 mL/minute): Approximately 40% higher systemic exposure; however, no obvious correlation between renal function and systemic exposure observed.

Severe renal impairment (Cl_cr 15–29 mL/minute): No clinically important effect on systemic exposure.

Distribution

Extent

Not known whether distributed into milk.

Plasma Protein Binding

Approximately 96%.

Elimination

Metabolism

Primarily metabolized by CYP3A4 and, to a lesser extent, CYP2C9; no known major metabolites.

Elimination Route

Eliminated in feces (approximately 78%) and urine (approximately 24%); approximately 77% eliminated as unchanged drug.

Half-life

Approximately 11 hours.

Special Populations

Not expected to be substantially removed by dialysis due to high protein binding.

Stability

Storage

Oral

Orally Disintegrating Tablets

20–25°C (excursions permitted to 15–30°C).

Actions

• Small molecule calcitonin gene-related peptide receptor (CGRP) receptor antagonist (gepants); binds to CGRP receptors with high affinity, blocking the binding of CGRP to the receptor and preventing subsequent receptor activation.

• CGRP is a potent vasodilator and pain-signaling neuropeptide that has been associated with migraine pathophysiology. CGRP and its receptors are located at sites that are relevant to migraine development such as the trigeminal neurons and are also widely distributed throughout the central and peripheral nervous systems as well as in nonneuronal tissues throughout the body.

• Increased serum CGRP concentrations observed in individuals during acute migraine attacks and return to normal after resolution of the migraine.

• Unlike 5-HT₁ receptor agonists (triptans) and ergot alkaloids, rimegepant does not appear to cause vasoconstriction.

Advice to Patients

• Importance of advising patients to read the manufacturer's patient information.

• Importance of instructing patients not to remove the tablet from the blister package until just before administering a dose, and to use dry hands when handling the tablet and to gently remove the tablet from the blister pack.

• Risk of hypersensitivity reactions, which may occur days after rimegepant administration. Importance of advising patients to seek immediate medical attention if they experience any symptoms of hypersensitivity reactions.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or are breast-feeding or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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